The phorbol ester tetradecanoylphorbol acetate (TPA) induces promyelocytic leukaemia cells to differentiate to macrophage-like cells in vitro. During the course of this differentiation, the cells adhere to the bottom of the culture dish, a process that requires an increase in cell surface glycosphingolipids (GSLs). We examined the cellular content of glucosylceramide (GlcCer), the simplest of the GSLs, in a TPA-treated leukaemia cell line, U937. Following TPA treatment, we observed a 3.5-fold increase in GlcCer levels that was caused by enhanced activity of ceramide glucosyltransferase (GlcT-1), which catalyses ceramide glycosylation. Furthermore, in TPA-treated cell GlcT-1 amounts were increased at both the mRNA and protein levels. We also found decreased activity of lactosylceramide synthase in TPA-treated cells, which could also contribute to the increase in cellular GlcCer content.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/jb/mvr058 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Glucosylceramide Synthase Inhibition in Combination with Aripiprazole Sensitizes Hepatocellular Cancer Cells to Sorafenib and Doxorubicin.
Int J Mol Sci
December 2024
Lipid Pathobiochemistry Group, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Hepatocellular carcinoma () is one of the leading causes of cancer deaths due to its late diagnosis and restricted therapeutic options. Therefore, the search for appropriate alternatives to commonly applied therapies remains an area of high clinical need. Here we investigated the therapeutic potential of the glucosylceramide synthase (GCS) inhibitor Genz-123346 and the cationic amphiphilic drug aripiprazole on the inhibition of Huh7 and Hepa 1-6 hepatocellular cancer cell and tumor microsphere growth.
View Article and Find Full Text PDFInhibiting UGCG prevents PRV infection by decreasing lysosome-associated autophage.
Int J Biol Macromol
January 2025
School of Food and Bioengineering, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan Province, People's Republic of China, Zhengzhou 450046, China. Electronic address:
Glucosylceramide synthase (UGCG) is a key enzyme that catalyzes the initial glycosylation step in the biosynthesis of glycosphingolipids (GSLs) derived from glucosylceramide. UGCG is closely associated with various cellular processes, including the cell cycle, angiogenesis, multidrug resistance, and pathogen invasion. In this study, a short hairpin RNA (shRNA) library designed to target key genes involved in the sphingolipid metabolic pathway was utilized to elucidate their roles in Pseudorabies Virus (PRV).
View Article and Find Full Text PDFGlucosylceramide synthase inhibitor ameliorates chronic inflammatory pain.
J Pharmacol Sci
December 2024
Laboratory of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan; Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan. Electronic address:
Article Synopsis
- - Gangliosides are important for functions in nerve cells, influencing processes like growth, communication, and degeneration.
- - Research indicated that mice given gangliosides made from glucosylceramide experienced heightened sensitivity to touch, known as mechanical allodynia.
- - The study found that using glucosylceramide inhibitors helped decrease this sensitivity during inflammation in mice, highlighting the potential of targeting gangliosides for pain relief.
UDP-glucose ceramide glucosyltransferase specifically upregulated in plasmacytoid dendritic cells regulates type I interferon production upon CpG stimulation.
Biochem Biophys Res Commun
November 2024
Core Research Facilities, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
Plasmacytoid dendritic cells (pDCs) are a distinct subset of DCs involved in immune regulation and antiviral immune responses. Recent studies have elucidated the metabolic profile of pDCs and reported that perturbations in amino acid metabolism can modulate their immune functions. Glycolipid metabolism is suggested to be highly active in pDCs; however, its significance remains unclear.
View Article and Find Full Text PDFDivergent effects of acute and chronic PPT1 inhibition in melanoma.
Autophagy
September 2024
Abramson Cancer Center and Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Macroautophagy/autophagy-lysosome function promotes growth and survival of cancer cells, making them attractive targets for cancer therapy. One intriguing lysosomal target is PPT1 (palmitoyl-protein thioesterase 1). PPT1 inhibitors derived from chloroquine block autophagy, have significant antitumor activity in preclinical models and are being developed for clinical trials.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!